Fig. 4

Potential points of action of flavonoids within JNK pathway. JNK is regulated by a variety of MAPKKK’s, including MEKK1/4 and apoptosis-stimulating kinase (ASK1), which is further regulated by GTPases and Rac1. Unlike the ERK pathway, the JNK cascade is strongly activated by stress signals such as UV and γ-radiation, oxidative stress and inflammatory cytokines. The MAPKK, MKK4/7, dually phosphorylates JNK within the Thr¹³⁸-Pro-Tyr-¹⁸⁵ motif (pTPpY) in the catalytic core of active JNK. Active JNK has been strongly linked to transcription-dependent apoptotic signalling, mainly through the activation of c-Jun and other AP-1 proteins including JunB, JunD and ATF-2